Self-assembly is a powerful, bottom-up strategy for the creation of complex nanostructures from smaller simple building blocks, which are guided by local interactions. The targeted formation of self-assembled structures has been implemented successfully across a broad swath of platforms, from enthalpically-mediated ligand-coated nanoparticles to entropic interactions. Here, we study two distinct platforms: (1) the molecular assembly of metal–organic frameworks (MOFs) and (2) the engineered assembly of magnetic handshake materials (MHM), both of which encode local interactions through a combination of bonds and shapes. We develop coarse-grained models for molecular dynamics simulations to study the self-assembly and analyze the final structures formed in detail. This enables us to abstract out both design rules for the creation of the building blocks as well as guidelines for synthesis conditions with which to obtain desired structures. (1) MOFs are a class of high-porosity materials with metallic nodes coordinated to large organic linker molecules, resulting in high-surface-area, open framework structures. While there are tens of thousands of MOFs currently synthesized, experimentalists often struggle to obtain large crystals, limiting both their application as well as the ability to understand the structure–processing–properties paradigms for MOFs. We use a set of coarse-grained models to simulate MOF growth; however, as in experiments, the resulting assemblies still suffer from poor crystallinity. Here, we address this by creating a seeded-growth protocol to assemble larger, defect-free crystals. (2) Magnetic handshake materials are a new platform that exhibits uniquely specific, strong, and long-range interactions between building blocks, leading to superior self-assembly behavior. We study the two-step formation of the hierarchical materials that magnetic handshake panels assemble, with panels first connecting face-to-face to form long, polymer-like chains, which then condense into stacks, connecting panels side-by-side. This assembly pathway is directly tied to the interaction length scale and patterning of the panels, allowing for tuning the hierarchy and strength of the interactions. The unifying theme across both systems is the importance of strategies to obtain defect-free structures: seeded growth for MOFs and hierarchical assembly in the case of the magnetic handshake materials.